Platelet-activating factor inactivation by local expression of platelet-activating factor acetyl-hydrolase modifies tumor vascularization and growth.
Articolo
Data di Pubblicazione:
2003
Abstract:
PURPOSE: Platelet-activating factor (PAF), a phospholipid mediator of inflammation, has been recently detected on tumor cells but its effect in tumor development is largely undefined. EXPERIMENTAL DESIGN: To address its potential role in tumor biology, we inhibited intratumor PAF activity by engineering tumor cell lines to express plasma PAF-acetylhydrolase (PAF-AH), the major PAF-inactivating enzyme, and studied their behavior in vitro and in vivo. RESULTS: When transfected with PAF-AH, KS-Imm human Kaposi's sarcoma cells implanted in SCID mice and B16F10 mouse melanoma cells implanted in syngenic C57Bl/6J mice showed significantly reduced vascularization and growth allowing longer survival compared with control tumors. The amounts of bioactive PAF extracted from PAF-AH-transfected tumors were significantly reduced. In vitro, expression of PAF-AH did not influence cell proliferation, whereas it inhibited PAF-dependent cell motility in Kaposi's sarcoma cells that express PAF-receptor but not in melanoma cells that did not express it. On the other hand, PAF-induced endothelial tubulogenesis in Matrigel was inhibited by incubation with supernatant from PAF-AH-transfected melanoma cells, indicating that PAF-AH inhibits in vitro neoangiogenesis. CONCLUSIONS: We demonstrated that in situ PAF inactivation affects tumor vascularization and growth through inhibition of neoangiogenesis and, in the case of cells expressing PAF receptor, also tumor cell motility.
Tipologia CRIS:
03A-Articolo su Rivista
Elenco autori:
BIANCONE L; CANTALUPPI V; L. DEL SORBO; RUSSO S; TJOELKER LW; CAMUSSI G
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